PROJECT SUMMARY The mission of the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) is to sustain a unique Findable-Accessible-Interoperable-Reusable living data resource of three-dimensional (3D) biomolecular structure information. PDB structures are the molecules of life. Knowledge of 3D structures (shapes) of biological macromolecules, how they evolved with time, and their functions are essential for understanding critical areas of science, including fundamental biology; health and disease of humans, animals, and plants; food and energy production; and other topics of concern to global prosperity and environmental sustainability. Structure data are equally important for biopharmaceutical and biotechnology companies, driving discovery of new therapeutics, biomaterials, and medical devices. RCSB PDB services span the entire PDB data lifecycle, encompassing Deposition/Biocuration, Archive Management/Access, Data Exploration, and Outreach/Education. RCSB PDB Archive Management/Access services safeguard the single global archive of >144,000 3D structures of biological macromolecules, with an estimated replacement cost of nearly $14 billion. RCSB PDB Deposition/Biocuration and Data Exploration services support >30,000 Data Depositors and >1 million Data Consumers worldwide. More than 620,000 researchers, educators, students, and members of the public use our award winning Outreach/Education Services. During 2019-2023, the RCSB PDB has three Specific Aims. Successful completion of these Specific Aims will entail further investments in cloud computing/storage, considerable software engineering, and modest recruitment of additional personnel to address three overarching challenges that confront the organization. Specific Aim 1: Scale RCSB PDB operational capabilities to meet projected growth in (i) new structures; (ii) average structure size and complexity; (iii) annual data download volume; and (iv) Users and User communities, and diversity thereof. Specific Aim 2: Scale RCSB PDB operational capabilities to meet projected growth in structure data and complexity coming from studies of molecular machines using two rapidly evolving experimental methods (serial femtosecond X-ray crystallography or SFX and 3DEM) that have already eclipsed some of our service capabilities. Specific Aim 3: Implement deposition-validation-biocuration, archiving, and online delivery/tooling for structure data from emerging structure determination methods that combine 3DEM and/or macromolecular crystallography with multiple measurement techniques not currently supported in the PDB. These Integrative/Hybrid Methods structures are in the vanguard of cell/organismal biology research. Continued access to PDB data and RCSB PDB Services will drive publication of innovative research across the biomedical sciences, drug discovery and development, patent applications, and innovations leading to discovery and development of life-changing biopharmaceutical products and formation of new US companies.